Abstract
Kidney stone disease (KSD) is a major clinical problem imposing a large burden for both healthcare and economy globally. In India, the prevalence of kidney stone disease is rapidly increasing. This study aimed to evaluate the association between genetic defects in vitamin D receptor (VDR), calcium sensing receptor (CaSR) and claudin 14 (CLDN14) genes and kidney stone disease in patients from eastern India. We enrolled 200 consecutive kidney stone patients (age 18–60 years) (cases) and their corresponding sex and age matched 200 normal individuals (controls). To identify genetic variants responsible for KSD, we performed sequence analysis of VDR, CaSR and CLDN14 genes. Four non-synonymous (rs1801725, rs1042636, rs1801726 and rs2228570), one synonymous (rs219780) and three intronic single nucleotide polymorphisms (SNPs) (rs731236, rs219777 and rs219778) were identified. Genotype and allele frequency analysis of these SNPs revealed that, rs1801725 (Ala986Ser), rs1042636 (Arg990Gly) of CaSR gene and rs219778, rs219780 (Thr229Thr) of CLDN14 gene were significantly associated with KSD. Serum calcium levels were significantly higher in subjects carrying 986Ser allele and calcium excretion was higher in subjects bearing 990Gly allele. In conclusion, rs1801725, rs1042636, rs219778 and rs219780 SNPs were associated with kidney stone risk in patients from the eastern part of India.
Highlights
Kidney stone is a solid crystal aggregation formed in the kidneys from dietary minerals in the urine
Our result revealed that individuals carrying both risk alleles showed 9.5 fold increase risk (p-
Our study revealed that individuals carrying 4 risk alleles showed approximately 8 fold increase risk (p- 0.04; Odds ratio = 8.29; 95% CI: 1.03–66.93) for the development of kidney stone disease compared to individuals carrying less number of risk alleles or no risk allele
Summary
Kidney stone is a solid crystal aggregation formed in the kidneys from dietary minerals in the urine. VDR, CaSR and CLDN14 Gene Polymorphisms in Kidney Stone Patients incidence and major problem for healthcare and the economy. Kidney stone formation is a multi-factorial urologic disorder resulting from the combined influence of epidemiological, biochemical and genetic risk factors [2]. The tendency of stone formation is largely attributed to primary renal calcium leak, excessive calcium absorption or an imbalance between bone resorption and formation. Vitamin D receptor (VDR) plays an important role in regulating calcium homeostasis by affecting bone resorption and increasing calcium absorption [3]. It has been reported that the intestine, bones and kidneys of genetic hypercalciuric stone-forming rats exhibited increased numbers of vitamin D receptor [4]. A growing amount of epidemiological evidence has suggested that allelic variation of VDR gene may be involved in the etiology of kidney stone disease [5]. Among them four (Apa I, Bsm I, Taq I and Fok I) are studied throughout the globe but with controversial results
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